Previous work in this Branch has elucidated the neuroanatomical pattern of c-fos mRNA expression with the development of amygdala kindled seizures. This project extends that line of investigation to the expression of mRNAs of peptides during kindling and their relationship to c-fos induction. mRNA levels of enkephalin, dynorphin, and thyrotropin releasing hormone (TRH) were measured by in situ hybridization at different stages of kindling. Enkephalin and TRH mRNAs increase, but dynorphin mRNA decreases with kindling. Each has a different pattern of activation or inhibition at the various stages of kindling. For instance, enkephalin mRNA increases in the entorhinal cortex after a stage 1 seizure and in the pyriform and entorhinal cortices after a stage 5 seizure, while TRH increases in both the pyriform and entorhinal cortices following stage 1 and 5 seizures. TRH also increases in the dentate gyrus. Dynorphin decreases in the dentate gyrus after stage 5. Changes in TRH and dynorphin are transient, and only enkephalin mRNA in the pyriform cortex remains elevated for at least two weeks. Interest- ingly, the pattern of TRH mRNA expression most closely resembles that of s-fos. This suggests that c-fos and TRH expression in kindling may be related and colocalized in certain populations of cells. Indeed, in situ double labeling of TRH mRNA with an oligonucleotide probe, and FOS protein and FOS-related antigens with an antibody demonstrates that the vast majority of FOS labelled cells are labelled with TRH mRNA following a kindled seizure. This suggests that FOS may act as a transcription factor for TRH during kindling.